National Vital Statistics Reports Volume 68, Number 3 March 21, 2019

Drug Overdose Deaths Involving Fentanyl, 2011–2016 by Merianne Rose Spencer, M.P.H., Margaret Warner, Ph.D., and Brigham A. Bastian, B.S., National Center for Health Statistics; James P. Trinidad, M.P.H., M.S., U.S. Food and Drug Administration; and Holly Hedegaard, M.D., M.S.P.H., National Center for Health Statistics

Abstract reporting over the study period did not change the trend patterns observed. Objectives—Fentanyl, a synthetic opioid, has been Conclusions—This report illustrates the rise in drug increasingly identified in drug overdose deaths. This report overdose deaths involving fentanyl from 2011 through 2016 describes trends in drug overdose deaths involving fentanyl by nationally, and by age, sex, race and ethnicity, and public health demographic characteristics and geographic regions from 2011 region. Understanding national trends and patterns for drug through 2016. overdose deaths involving fentanyl may inform public health Methods—Drug overdose deaths were identified from policies and practices. the National Vital Statistics System—Mortality (NVSS–M) multiple cause-of-death files (2011–2016) using International Keywords: National Vital Statistics System • national trends • Classification of Diseases, 10th Revision underlying causes of mortality • death certificate literal text death (codes X40–X44, X60–X64, X85, or Y10–Y14). NVSS–M records for drug overdose deaths were linked with literal text Introduction from death certificates. Drug overdose deaths involving fentanyl were identified using a methodology established collaboratively Fentanyl is a synthetic opioid that has been involved by the National Center for Health Statistics and U.S. Food and increasingly in drug overdose deaths (1–11). In 2011 and 2012, Drug Administration—referred to as the Drugs Mentioned fentanyl was involved in roughly 1,600 drug overdose deaths with Involvement (DMI) methodology—supplemented with each year, but from 2012 through 2014, the number of drug search terms identified using text analytics software. Fentanyl overdose deaths involving fentanyl more than doubled each year involvement was determined by the presence of any string term (1). State-based analyses suggest that the recent increase in or phrase listing fentanyl, or any fentanyl metabolite, precursor, overdose deaths involving fentanyl may be related to increased analog, or misspelling identified in the death certificate literal text availability of illicitly manufactured fentanyl (3,4,9–11). fields (i.e., the causes of death from Part I, significant conditions Illicitly manufactured fentanyl includes various analogs (e.g., contributing to death from Part II, and a description of how acetylfentanyl, carfentanil, furanyl fentanyl) that vary in potency the injury occurred). Trends were evaluated using the National and can be lethal in very low concentrations (3). Cancer Institute’s Joinpoint Regression Program. National mortality statistics on drug overdose deaths have traditionally used the Results—The number of drug overdose deaths involving International Classification of Diseases, fentanyl was stable in 2011 (1,663) and 2012 (1,615), and began 10th Revision (ICD–10) to classify and monitor drugs involved to increase in 2013, rising to 18,335 deaths in 2016. The age- in deaths (12). However, ICD–10 is limited to broader categories adjusted rate increased from 0.5 per 100,000 standard population (e.g., synthetic opioids other than methadone) that make it in 2011 to 5.9 per 100,000 in 2016, with the increase starting in difficult to identify deaths involving specific drugs of interest 2013 (0.6 in 2013 to 1.3 in 2014 and 2.6 in 2015). Numbers and (e.g., fentanyl or illicitly manufactured fentanyl analogs). rates increased for all sex, age, and racial and ethnic subgroups, The National Center for Health Statistics (NCHS) and the U.S. and most public health regions. Adjustment for improved drug Food and Drug Administration (FDA) collaboratively developed methods, referred to as the Drugs Mentioned with Involvement (DMI) methodology, to analyze literal text data from death

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Center for Health Statistics National Vital Statistics System

NCHS reports can be downloaded from: https://www.cdc.gov/nchs/products/index.htm. This report was revised on April 3, 2019, to correct for the inadvertent omission of North Carolina from the list of states in Region 4. 2 National Vital Statistics Reports, Vol. 68, No. 3, March 21, 2019 certificates to identify specific drugs involved in deaths (13). A are assumed to be involved in the death unless contextual recent study using the DMI methodology found that fentanyl was information suggests otherwise (13). For example, “METHICILLIN the ninth most frequently mentioned drug involved in overdose RESISTANT STAPHYLOCOCCUS AUREUS INFECTION” does deaths in 2013 and the most frequently mentioned drug in 2016 not suggest drug involvement in mortality, but rather a type of (2). It also showed that deaths involving fentanyl often involved bacterial infection. Similarly, the phrase “NOT DRUG RELATED” other drugs. For example, in 2016, nearly 70% of deaths clearly indicates that drugs were not involved in the death even involving fentanyl also involved one or more other drugs, such though “DRUG” is included in the phrase. as heroin or cocaine (2). To supplement the DMI methodology, SAS Contextual This report describes the trends in drug overdose deaths Analysis software (18) was used to identify additional search involving fentanyl from 2011 through 2016, using mortality data terms. Linguistic rules were defined to search for new drug from the National Vital Statistics System linked to literal text misspellings; precursors; metabolites; analogs of fentanyl, information from death certificates. Temporal trends, geographic including those containing special characters, numbers, patterns, and differences among demographic groups are and dashes; and to identify forms that may be illicit (e.g., presented. acetylfentanyl, carfentanil) or are brand or prescription forms of fentanyl (e.g., duragesic, sufentanil, remifentanil). The additional Methods search terms identified using the contextual software were incorporated into the DMI methodology and are described in the Technical Notes. With the expanded list of search terms, the total Data sources number of drug overdose deaths identified as involving fentanyl This descriptive study analyzed National Vital Statistics was slightly higher than previously reported (7 deaths in 2011, System mortality (NVSS–M) multiple cause-of-death data from 10 deaths in 2012, 14 deaths in 2013, and 23 deaths in 2014) 2011 through 2016. NVSS–M contains information extracted (1). from death certificates on cause of death and demographic and geographic factors (14). The study population was limited to U.S. Analysis residents. Drug overdose deaths were identified using ICD–10 For this report, the label “drug overdose deaths involving underlying cause-of-death codes X40–X44, X60–X64, X85, and fentanyl” includes drug overdose deaths involving fentanyl, Y10–Y14. These underlying-cause codes identify the deaths due whether prescription or illicitly manufactured, as well as deaths to acute toxicity from drugs (i.e., drug overdose) rather than to involving any fentanyl metabolites, precursors, or analogs as chronic exposure leading to death (e.g., liver toxicity) or adverse identified in the death certificate literal text (see Technical Notes). effects from therapeutic or prophylactic dosages of drugs. Drug The numbers and rates for drug overdoses involving fentanyl overdose deaths include all intents (i.e., unintentional, suicide, were calculated and compared by demographic and geographic homicide, and undetermined intent). Use of these underlying region. Bridged-race vintage postcensal resident population cause-of-death codes is consistent with other NCHS publications estimates were used to calculate death rates (14). Age-adjusted on drug overdose deaths and facilitates comparisons with other death rates were calculated using the direct method and the 2000 analyses using ICD–10-coded data (1,2,15). standard U.S. population (14). Unless otherwise noted, rates in NVSS–M records for drug overdose deaths were linked the text refer to age-adjusted rates. to literal text data from death certificates. The literal text is the Geographic patterns in overdose deaths involving fentanyl written information provided by the medical certifier, usually are presented by the U.S. Department of Health and Human a medical examiner or coroner in the case of drug overdose Services (HHS) 10 public health regions. These regions are used deaths, that describes the cause of death as well as other factors for public health prevention, preparedness, and agency-wide or circumstances that contributed to the death (16,17). Literal coordination of HHS programs and policies (19). These regions, text from three fields of the death certificate—the causes of excluding U.S. territories, are: death from Part I, the other significant conditions contributing to death from Part II, and the description of how the injury • Region 1—Connecticut, Maine, Massachusetts, New occurred—was analyzed to identify the specific drugs involved Hampshire, Rhode Island, Vermont in the overdose death. • Region 2—New Jersey, New York, New York City • Region 3—Delaware, District of Columbia, Maryland, Identifying drug overdose deaths involving Pennsylvania, Virginia, West Virginia fentanyl • Region 4—Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina, Tennessee This report used the DMI methodology (13) informed by • Region 5—Illinois, Indiana, Michigan, Minnesota, Ohio, the results from an exploratory analysis of the literal text using Wisconsin SAS Contextual Analysis software (18). The DMI methodology • Region 6—Arkansas, Louisiana, New Mexico, Oklahoma, (13) searches the literal text fields of NVSS–M data for mentions Texas of drugs and for terms that provide context about involvement • Region 7—Iowa, Kansas, Missouri, Nebraska of the drug in the death (i.e., whether the drug contributed to the death). Drugs mentioned in the death certificate literal text National Vital Statistics Reports, Vol. 68, No. 3, March 21, 2019 3

• Region 8—Colorado, Montana, North Dakota, South Results Dakota, Utah, Wyoming • Region 9—Arizona, California, Hawaii, Nevada • Region 10—Alaska, Idaho, Oregon, Washington Number and percentage of drug overdose deaths involving fentanyl Trends in rates for drug overdose deaths involving fentanyl were evaluated using the National Cancer Institute’s Joinpoint Annually, the number of drug overdose deaths involving Regression Program Version 4.6.0.0 (20). Joinpoint software fentanyl was stable in 2011 (1,663) and 2012 (1,615), and fitted weighted least-squares regression models to the rates began to increase in 2013 (1,919), rising to 18,335 deaths in on the log transform scale. Allowing one observed time point 2016 (Table 1). From 2013 through 2016, the number of deaths at each end and two for the middle line segments, the Grid approximately doubled each year. From 2011 through the third Search Algorithm searched for a maximum of two joinpoints at quarter of 2013, there were fewer than 500 fentanyl-involved an overall alpha level of p < 0.05 (21). Pairwise comparisons deaths per quarter (Figure 1, Table 1). Beginning in the last of trend segments among subgroups were also analyzed, with quarter of 2013 through 2016, the number of deaths involving Bonferonni adjustment (20). Rates between subgroups were fentanyl increased nearly every quarter to more than 5,800 compared using a z test at the 0.05 level of significance (14). deaths. Unless otherwise stated, any mention of an increase in rates indicates a statistically significant change. Crude and age-adjusted rates of drug overdose deaths involving fentanyl Assessment for improved reporting on death The age-adjusted rate of drug overdose deaths involving certificates fentanyl was 0.5 per 100,000 in 2011 and 2012, and approximately The ICD–10 multiple-cause codes T36–T50.8 provide doubled each year from 0.6 (2013) to 1.3 (2014) to 2.6 (2015) information on the types of drugs or drug classes involved to 5.9 (2016) (Figure 2, Table 2). From 2011 through 2013, there in the death. The ICD–10 multiple-cause code T50.9 was no statistical change in the age-adjusted rates, but from indicates a nonspecific reference to a drug (e.g., “multidrug,” 2013 through 2016, the rates increased on average by about “polypharmacy,” “drug”). The percentage of deaths with an 113% per year. The crude rates were similar to the age-adjusted underlying cause of X40–X44, X60–X64, X85, or Y10–Y14 that rates for the study period. had a multiple-cause code of T36–T50.8 is a measure of the specificity of reporting drugs or drug classes in drug overdose Rates of drug overdose deaths involving deaths. This measure was used to assess possible changes in fentanyl by sex of decedent reporting of specific drugs and drug classes through the years of the study. The percentage of drug overdose deaths coded with For males, age-adjusted rates for drug overdose deaths were T36–T50.8 increased each year (75.0% in 2011, 76.0% in 2012, stable from 2011 through 2013, and then increased by 125.6% 77.9% in 2013, 80.7% in 2014, 83.1% in 2015, and 85.4% in per year from 2013 through 2016 (Figure 3, Tables 2 and 3). 2016) (21,22). For females, the age-adjusted rates increased exponentially from To assess the possible impact of lower reporting of specific 2011 through 2016. In 2011, 2012, and 2013, the rates for males drugs in the years prior to 2016, an adjustment factor accounting and females were similar at 0.6 to 0.7 per 100,000 for males, for improved reporting of specific drugs over the time period and 0.4 to 0.5 for females. Starting in 2013, the rates diverged, was applied to each age-adjusted rate for drug overdose deaths with the rate for males increasing more rapidly than the rate for involving fentanyl (i.e., by year, sex, age, race and ethnicity, and females. By 2016, the rate for males (8.6) was 2.8 times the rate public health region). The adjustment factor assumed that the for females (3.1). specificity of drug reporting had remained constant from 2011 through 2016 at the 2016 drug specificity rate; the adjustment Rates of drug overdose deaths involving factor was recalculated and applied to each age-adjusted rate fentanyl by age group for the stratified analyses (i.e., demographic and geographic groups). Results from this analysis show similar trends for Exponential increases in rates from 2011 through 2016 both the observed and adjusted values (see Technical Notes). were observed among all age groups (Figure 4, Tables 2 and 3). The following results reflect the numbers and rates based on The largest average annual percent change from 2011 through observed values. The number of drug overdose deaths involving 2016 occurred among young adults aged 25–34 (100.0% per any particular drug in any particular year should be considered year) and 15–24 (93.9% per year). The smallest average annual the minimum number, as there may be additional deaths in percent change occurred among adults aged 65 and over (41.6% which the drug was involved but not specified on the death per year). The rate for adults aged 35–44 was stable from 2011 certificate literal text. All results should be interpreted in light of through 2013, then increased by 123.7% per year from 2013 the improved reporting of specific drugs in the literal text over through 2016. In 2016, the rates were highest among adults aged time. 25–34 and 35–44 at 13.4 and 11.4 per 100,000, respectively. 4 National Vital Statistics Reports, Vol. 68, No. 3, March 21, 2019

,000

,000

4,000

3,000 Numer of deaths

2,000

1,000

1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 2011 2012 2013 2014 201 201 NTS: rug overdose deaths are identified using nternatonal Classfcaton of seases t eson underling causeofdeath codes 4044, 04, , and 1014. eaths ma involve other drugs in addition to fentanl. Caution should e used when comparing numers across ears. The reporting of at least one specific drug or drug class in the literal text, as identified multiple causeofdeath codes T3T0., improved from .0 of drug overdose deaths in 2011 to .4 in 201. SRC: NCHS, National Vital Statistics Sstem, ortalit files lined with death certificate literal text.

Figure 1. Number of drug overdose deaths involving fentanyl, by quarter: United States, 2011–2016

Rates of drug overdose deaths involving Rates of drug overdose deaths involving fentanyl by race and ethnicity fentanyl by public health region The age-adjusted rates for drug overdose deaths involving Rates of drug overdose deaths involving fentanyl increased fentanyl increased exponentially among all the racial and exponentially from 2011 through 2016 for most public health ethnic subgroups examined (Figure 5, Tables 2 and 3). Rates regions (Figure 6, Tables 2 and 3). The greatest rate increases for non-Hispanic white persons ranged from 0.7 to 0.8 per were in Region 1 (CT, ME, MA, NH, RI, and VT), Region 2 (NJ, 100,000 from 2011 through 2013, then increased by 108.8% NY, and NYC), Region 3 (DE, DC, MD, PA, VA, and WV), and from 2013 through 2016. Non-Hispanic black persons had the Region 5 (IL, IN, MI, MN, OH, and WI), which increased 113.9%, largest annual percentage increase in rates from 2011 through 110.9%, 103.6%, and 102.2% per year, respectively. Rates were 2016 (140.6% per year), followed by Hispanic persons (118.3% similar across all public health regions in 2011. In 2016, the rates per year). Rates for non-Hispanic white persons were greater for Regions 1, 2, 3, 4, and 5 were higher than for Regions 6, 8, than other subgroups throughout the study period. The rates 9, and 10. In 2016, rates ranged from 0.8 per 100,000 (Region for non-Hispanic black and Hispanic persons were similar from 9) to 19.8 (Region 1). 2011 through 2013, then diverged from 2014 through 2016. In 2016, the rates were highest among non-Hispanic white persons Discussion (7.7), followed by non-Hispanic black (5.6) and Hispanic (2.5) persons. This report illustrates the rise in drug overdose deaths involving fentanyl in the United States from 2011 through 2016. The number of drug overdose deaths involving fentanyl increased from 1,663 in 2011 to 18,335 in 2016. Beginning in the fourth quarter of 2013, the number of deaths increased every quarter. From 2013 through 2014, the death rate more than doubled, National Vital Statistics Reports, Vol. 68, No. 3, March 21, 2019 5

10 Age adusted Crude1

2 Females

eaths per 100,000 standard population eaths per 100,000 standard population

ales

2011 2012 2013 2014 201 201 2011 2012 2013 2014 201 201 ncreasing trends 2013201 for drug overdose death rates per 100,000 are ncreasing trend for 2013201 is statisticall significant p 0.0. statisticall significant p 0.0. 2ncreasing trend for 2011201 is statisticall significant p 0.0. NTS: rug overdose deaths are identified using nternatonal Classfcaton of NTS: rug overdose deaths are identified using nternatonal Classfcaton of seases t eson underling causeofdeath codes 4044, 04, , seases t eson underling causeofdeath codes 4044, 04, , and 1014. eaths ma involve other drugs in addition to fentanl. Caution should and 1014. eaths ma involve other drugs in addition to fentanl. eath rates are e used when comparing numers across ears. The reporting of at least one age adusted. Caution should e used when comparing numers across ears. The specific drug or drug class in the literal text, as identified multiple causeofdeath reporting of at least one specific drug or drug class in the literal text, as identified codes T3T0., improved from .0 of drug overdose deaths in 2011 t o .4 multiple causeofdeath codes T3T0., improved from .0 of drug overdose in 201. deaths in 2011 to .4 in 201. SRC: NCHS, National Vital Statistics Sstem, ortalit files lined with death SRC: NCHS, National Vital Statistics Sstem, ortalit files lined with death certificate literal text. certificate literal text.

Figure 2. Crude and age-adjusted rates for drug Figure 3. Age-adjusted rates for drug overdose deaths overdose deaths involving fentanyl, by year: involving fentanyl, by sex of the decedent: United States, 2011–2016 United States, 2011–2016 nearly doubled again from 2014 through 2015, and more than testing is performed, which substances are tested for, and the doubled again from 2015 through 2016. interpretation of the test results, can impact whether fentanyl is The rate of drug overdose deaths involving fentanyl detected and reported on the death certificate. Because of these increased exponentially for both sexes, with the rate increasing limitations, the number of drug overdose deaths involving any more rapidly for males than for females. Rates also increased particular drug in any particular year should be considered the exponentially across all age groups, with the greatest increases minimum number, as there may be additional deaths in which among those aged 15–24 and 25–34. Exponential increases the drug was involved but not specified on the death certificate were also seen for rates among race and ethnicity groups. literal text. Non-Hispanic black persons had the largest annual percentage Variations in the way drug overdose deaths are reported on increase in rates, followed by Hispanic persons, while in 2016, the death certificates, including the level of detail on the specific the rate was highest for non-Hispanic white persons. Rates drugs involved, impacts comparability. Trends in rates should increased exponentially for most public health regions, however, be interpreted in light of the improvements in the quality of the the increase was greatest in Regions 1, 2, 3, and 5 (i.e., East data during the study period. For example, some of the observed Coast and Upper Midwest). increases in the rates are likely attributable to improvements in reporting. During the study period, the reporting of at least Limitations one specific drug in the literal text improved from 75% of drug overdose deaths in 2011 to 85% of drug overdose deaths in 2016 Monitoring national trends in drug overdose deaths depends (2,22). To account for improved reporting of specific drugs over on the quality and completeness of information provided on the time period, an adjustment factor, which took into account death certificates. Variation in death investigation, autopsy, and what the drug overdose death rate involving fentanyl would have toxicology practices across medicolegal death investigation been had the drug specificity been uniform from 2011 through jurisdictions contributes to inconsistencies in how the manner 2016, was applied to the rates. The adjustments for improved and cause of death are reported (23,24). For example, differences reporting did not change the patterns observed. in toxicological testing practices, such as when and how the 6 National Vital Statistics Reports, Vol. 68, No. 3, March 21, 2019

1

2341

12 3442

9 441

4 1241 eaths per 100,000 population

and over1

2011 2012 2013 2014 201 201 ncreasing trend for 2011201 is statisticall significant p 0.0. 2ncreasing trend for 2013201 is statisticall significant p 0.0. NTS: rug overdose deaths are identified using nternatonal Classfcaton of seases t eson underling causeofdeath codes 4044, 04, , and 1014. eaths ma involve other drugs in addition to fentanl. eath rates are age adusted. Caution should e used when comparing numers across ears. The reporting of at least one specific drug or drug class in the literal text, as identified multiple causeofdeath codes T3T0., improved from .0 of drug overdose deaths in 2011 to .4 in 201. SRC: NCHS, National Vital Statistics Sstem, ortalit files lined with death certificate literal text.

Figure 4. Rates for drug overdose deaths involving fentanyl, by age group: United States, 2011–2016

Hispanic2

eaths per 100,000 standard population NonHispanic white1

NonHispanic lac2

2011 2012 2013 2014 201 201 ncreasing trend for 2013201 is statisticall significant p 0.0. 2ncreasing trend for 2011201 is statisticall significant p 0.0. NTS: rug overdose deaths are identified using nternatonal Classfcaton of seases t eson underling causeofdeath codes 4044, 04, , and 1014. eaths ma involve other drugs in addition to fentanl. eath rates are age adusted. Caution should e used when comparing numers across ears. The reporting of at least one specific drug or drug class in the literal text, as identified multiple causeofdeath codes T3T0., improved from .0 of drug overdose deaths in 2011 to .4 in 201. SRC: NCHS National Vital Statistics Sstem, ortalit files lined with death certificate literal text.

Figure 5. Age-adjusted rates for drug overdose deaths involving fentanyl, by race and ethnicity: United States, 2011–2016 National Vital Statistics Reports, Vol. 68, No. 3, March 21, 2019 7

2011 2012 2013 2014 201 201 20

1

10

Region 11 Region 21 Region 31 Region 42 Region 1 20

1

eaths per 100,000 standard population 10

Region 1 Region 1 Region Region 9 Region 101 ncreasing trend for 2011201 is statisticall significant p 0.0. 2ncreasing trend for 2013201 is statisticall significant p 0.0. NTS: Trends in rates from 2011 through 201 were evaluated using the oinpoint Regression rogram Version 4..0.0. See Tale 3 in the report for details. ulic health regions are defined as: Region 1 CT, , A, NH, R, and VT, Region 2 N, N, and NC, Region 3 , C, , A, VA, and V, Region 4 A, F, A, , S, NC, SC, and TN, Region , N, , N, H, and , Region AR, A, N, , and T, Region A, S, , and N, Region C, T, N, S, T, and , Region 9 A, CA, H, and NV, and Region 10 A, , R, and A. rug overdose deaths are identified using nternatonal Classfcaton of seases t eson underling causeofdeath codes 4044, 04, , and 1014. eaths ma involve other drugs in addition to fentanl. eath rates are age adusted. SRC: NCHS, National Vital Statistics Sstem, ortalit files lined with death certificate literal text.

Figure 6. Age-adjusted rates for drug overdose deaths involving fentanyl, by public health region: United States, 2011–2016

The absence of drug-specific information on the death Conclusion certificate does not mean that fentanyl was not present; rather, it may suggest that toxicology tests were not performed or were Fentanyl is increasingly involved in drug overdose deaths inadequate to detect the drug. Also, new fentanyl analogs are nationally. This report uses NVSS–M data, enhanced with literal being identified with increasing frequency and are often lethal in text from death certificates, to provide a picture of temporal very low concentrations. Detection of these substances requires trends, demographic characteristics, and geographic patterns new testing materials and continuous recalibration of toxicology of fentanyl-involved drug overdose deaths in the United States laboratory equipment (16), both of which can be complicated from 2011 through 2016. and expensive, thus further contributing to variation in death reporting across the country. References The need to understand the factors influencing overdoses and deaths involving fentanyl has resulted in collaboration 1. Warner M, Trinidad JP, Bastian BA, Miniño AM, Hedegaard H. Drugs most frequently involved in drug overdose deaths: United among public health agencies, medical examiners and coroners, States, 2010–2014. National Vital Statistics Reports; vol 65 no 10. and public safety agencies. These collaborations will contribute Hyattsville, MD: National Center for Health Statistics. 2016. to better detection and reporting on death certificates, which in 2. Hedegaard H, Bastian BA, Trinidad JP, Spencer M, Warner M. turn, will help improve quality of local, state, and national vital Drugs most frequently involved in drug overdose deaths: United statistics data. States, 2011–2016. National Vital Statistics Reports; vol 67 no 9. Hyattsville, MD: National Center for Health Statistics. 2018. 3. Peterson AB, Gladden RM, Delcher C, Spies E, Garcia-Williams A, Wang Y, et al. Increases in fentanyl-related overdose deaths— Florida and Ohio, 2013–2015. MMWR Morb Mortal Wkly Rep 65(33):844–9. 2016. 8 National Vital Statistics Reports, Vol. 68, No. 3, March 21, 2019

4. Gladden RM, Martinez P, Seth P. Fentanyl law enforcement WONDER Online Database, released December 2017. Data from submissions and increases in synthetic opioid-involved overdose the Multiple Cause of Death Files, 1999–2016, as compiled from deaths—27 states, 2013–2014. MMWR Morb Mortal Wkly Rep data provided by the 57 vital statistics jurisdictions through the 65(33):837–43. 2016. Vital Statistics Cooperative Program. Available from: 5. Frank RG, Pollack HA. Addressing the fentanyl threat to public https://wonder.cdc.gov/mcd-icd10.html. health. N Engl J Med 376(7):605–7. 2017. 23. Warner M, Paulozzi LJ, Nolte KB, Davis GG, Nelson LS. State 6. Centers for Disease Control and Prevention. CDC Health Alert variation in certifying manner of death and drugs involved in drug Network (HAN) update: Rising numbers of deaths involving intoxication deaths. AFP Journal 3(2):231–7. 2013. fentanyl and fentanyl analogs, including carfentanil, and increased 24. Hanzlick RL. A perspective on medicolegal death investigation in usage and mixing of non-opioids [press release]. July 11, 2018. the United States: 2013. Acad Forensic Pathol 4(1):2–9. 2014. Available from: https://content.govdelivery.com/accounts/USCDC/ 25. United States Drug Enforcement Administration. Scientific bulletins/1fdd63b. Working Group for the Analysis of Seized Drugs. Available from: 7. Jones CM, Einstein EB, Compton WM. Changes in synthetic opioid http://swgdrug.org/monographs.htm. involvement in drug overdose deaths in the United States, 26. U.S. Food and Drug Administration, National Library of Medicine. 2010–2016. JAMA 319(17):1819–21. 2018. Substance Registration System—Unique ingredient identifier. 8. Rudd RA, Seth P, David F, Scholl L. Increases in drug and opioid- Available from: https://fdasis.nlm.nih.gov/srs. involved overdose deaths—United States, 2010–2015. MMWR Morb Mortal Wkly Rep 65(50–51):1445–52. 2016. 9. O'Donnell JK, Halpin J, Mattson CL, Goldberger BA, Gladden RM. List of Detailed Tables Deaths involving fentanyl, fentanyl analogs, and U–47700—10 1. Number of drug overdose deaths involving fentanyl and percent states, July–December 2016. MMWR Morb Mortal Wkly Rep of the annual total, by year and quarter: United States, 2011– 66(43):1197–1202. 2017. 2016 ...... 9 10. Somerville NJ, O'Donnell J, Gladden RM, Zibbell JE, Green TC, 2. Numbers and crude and age-adjusted rates for drug Younkin M, et al. Characteristics of fentanyl overdose— overdose deaths involving fentanyl, by sex, age, race and Massachusetts, 2014–2016. MMWR Morb Mortal Wkly Rep Hispanic origin, and public health region: United States, 66(14):382–6. 2017. 2011–2016 ...... 10 11. Suzuki J, El-Haddad S. A review: Fentanyl and non-pharmaceutical 3. Trends in age-adjusted rates for drug overdose deaths involving fentanyls. Drug and Alcohol Depend 171:107–16. 2017. fentanyl, by sex, age, race and Hispanic origin, and public health 12. World Health Organization. International statistical classification region: United States, 2011–2016 ...... 12 of diseases and related health problems, 10th revision (ICD–10). 2nd ed. Geneva, Switzerland. 2004. 13. Trinidad JP, Warner M, Bastian BA, Miniño AM, Hedegaard H. Using literal text from the death certificate to enhance mortality statistics: Characterizing drug involvement in deaths. National Vital Statistics Reports; vol 65 no 9. Hyattsville, MD: National Center for Health Statistics. 2016. 14. Xu JQ, Murphy SL, Kochanek KD, Bastian B, Arias E. Deaths: Final data for 2016. National Vital Statistics Reports; vol 67 no 5. Hyattsville, MD: National Center for Health Statistics. 2018. 15. Hedegaard H, Warner M, Miniño AM. Drug overdose deaths in the United States, 1999–2016. NCHS Data Brief, no 294. Hyattsville, MD: National Center for Health Statistics. 2017. 16. Davis GG. National Association of Medical Examiners position paper: Recommendations for the investigation, diagnosis, and certification of deaths related to opioid drugs. J Med Toxicol 10(1):100–6. 2014. 17. National Center for Health Statistics. Medical examiners' and coroners' handbook on death registration and fetal death reporting. 2003. 18. SAS Institute, Inc. SAS contextual analysis (Release 14.1 edition) [computer software]. 2016. 19. U.S. Department of Health and Human Services. Regional offices. Available from: https://www.hhs.gov/about/agencies/regional- offices/index.html. 20. National Cancer Institute. Joinpoint Regression Program (Version 3.4.3) [computer software]. 2010. 21. Ingram DD, Malec DJ, Makuc DM, Kruszon-Moran D, Gindi RM, Albert M, et al. National Center for Health Statistics Guidelines for Analysis of Trends. National Center for Health Statistics. Vital Health Stat 2(179). 2018. Available from: https://www.cdc.gov/ nchs/data/series/sr_02/sr02_179.pdf. 22. Centers for Disease Control and Prevention, National Center for Health Statistics. About multiple cause of death, 1999–2017. CDC National Vital Statistics Reports, Vol. 68, No. 3, March 21, 2019 9

Table 1. Number of drug overdose deaths involving fentanyl and percent of the annual total, by year and quarter: United States, 2011–2016

Year and quarter Number Percent

2011 1,663 100.0 Quarter 1 449 27.0 Quarter 2 432 26.0 Quarter 3 391 23.5 Quarter 4 391 23.5 2012 1,615 100.0 Quarter 1 398 24.6 Quarter 2 412 25.5 Quarter 3 397 24.6 Quarter 4 408 25.3 2013 1,919 100.0 Quarter 1 438 22.8 Quarter 2 461 24.0 Quarter 3 385 20.1 Quarter 4 635 33.1 2014 4,223 100.0 Quarter 1 1,031 24.4 Quarter 2 861 20.4 Quarter 3 925 21.9 Quarter 4 1,406 33.3 2015 8,251 100.0 Quarter 1 1,863 22.6 Quarter 2 2,009 24.3 Quarter 3 2,005 24.3 Quarter 4 2,374 28.8 2016 18,335 100.0 Quarter 1 3,617 19.7 Quarter 2 4,197 22.9 Quarter 3 4,673 25.5 Quarter 4 5,848 31.9

NOTES: Drug overdose deaths are identified using International Classification of Diseases, 10th Revision underlying cause-of-death codes X40–X44, X60–X64, X85, and Y10–Y14. Deaths may involve other drugs in addition to fentanyl. Caution should be used when comparing numbers across years. The reporting of at least one specific drug or drug class in the literal text, as identified by multiple cause-of-death codes T36–T50.8, improved from 75.0% of drug overdose deaths in 2011 to 85.4% in 2016. SOURCE: NCHS, National Vital Statistics System, Mortality files linked with death certificate literal text. 10 National Vital Statistics Reports, Vol. 68, No. 3, March 21, 2019

Table 2. Numbers and crude and age-adjusted rates for drug overdose deaths involving fentanyl, by sex, age, race and Hispanic origin, and public health region: United States, 2011–2016

Characteristic 2011 2012 2013 2014 2015 2016

Number All drug overdose deaths 1,663 1,615 1,919 4,223 8,251 18,335 Sex Male 916 912 1,107 2,827 5,945 13,413 Female 747 703 812 1,396 2,306 4,922 Age group (years) 15–24 129 110 160 453 927 1,924 25–34 325 332 415 1,223 2,691 5,976 35–44 378 350 399 992 1,990 4,615 45–54 505 498 552 971 1,605 3,531 55–64 264 261 325 489 897 1,980 65 and over 55 61 66 91 135 299 Race and Hispanic origin Non-Hispanic white 1,507 1,462 1,684 3,569 6,855 14,236 Non-Hispanic black 63 62 111 358 800 2,357 Hispanic 60 50 95 223 447 1,399 Public health region¹ 1 (CT, ME, MA, NH, RI, VT) 80 77 160 775 1,621 2,745 2 (NJ, NY, NYC) 114 115 180 328 830 2,241 3 (DE, DC, MD, PA, VA, WV) 209 191 283 596 1,163 3,545 4 (AL, FL, GA, KY, MS, NC, SC, TN) 406 405 433 906 1,694 3,460 5 (IL, IN, MI, MN, OH, WI) 299 274 290 910 2,074 4,790 6 (AR, LA, NM, OK, TX) 147 166 167 224 257 393 7 (IA, KS, MO, NE) 85 103 120 133 221 489 8 (CO, MT, ND, SD, UT, WY) 103 88 80 117 98 145 9 (AZ, CA, HI, NV) 163 125 138 158 215 411 10 (AK, ID, OR, WA) 57 71 68 76 78 116 Crude rate (per 100,000) All drug overdose deaths 0.53 0.51 0.61 1.32 2.57 5.67 Sex Male 0.60 0.59 0.71 1.80 3.76 8.43 Female 0.47 0.44 0.51 0.86 1.41 3.00 Age group (years) 15–24 0.29 0.25 0.36 1.03 2.11 4.42 25–34 0.78 0.78 0.97 2.81 6.10 13.38 35–44 0.93 0.86 0.99 2.45 4.90 11.40 45–54 1.13 1.12 1.26 2.23 3.72 8.25 55–64 0.69 0.68 0.83 1.22 2.19 4.78 65 and over 0.13 0.14 0.15 0.20 0.28 0.61 Race and Hispanic origin Non-Hispanic white 0.75 0.73 0.84 1.78 3.41 7.07 Non-Hispanic black 0.16 0.15 0.27 0.87 1.91 5.59 Hispanic 0.12 0.09 0.18 0.40 0.79 2.43

See footnotes at end of table. National Vital Statistics Reports, Vol. 68, No. 3, March 21, 2019 11

Table 2. Numbers and crude and age-adjusted rates for drug overdose deaths involving fentanyl, by sex, age, race and Hispanic origin, and public health region: United States, 2011–2016—Con.

Characteristic 2011 2012 2013 2014 2015 2016

Public health region¹ Crude rate (per 100,000) 1 (CT, ME, MA, NH, RI, VT) 0.53 0.53 1.07 5.54 11.65 19.79 2 (NJ, NY, and NYC) 0.39 0.39 0.63 1.12 2.91 7.88 3 (DE, DC, MD, PA, VA, WV) 0.70 0.64 0.94 1.95 3.88 11.87 4 (AL, FL, GA, KY, MS, NC, SC, TN) 0.67 0.66 0.71 1.48 2.79 5.70 5 (IL, IN, MI, MN, OH, WI) 0.57 0.52 0.55 1.83 4.16 9.63 6 (AR, LA, NM, OK, TX) 0.39 0.42 0.43 0.55 0.62 0.97 7 (IA, KS, MO, NE) 0.61 0.81 0.91 1.02 1.66 3.78 8 (CO, MT, ND, SD, UT, WY) 0.95 0.77 0.69 1.05 0.87 1.27 9 (AZ, CA, HI, NV) 0.33 0.24 0.26 0.29 0.42 0.81 10 (AK, ID, OR, WA) 0.43 0.53 0.48 0.58 0.56 0.89 Age-adjusted rate (per 100,000) All drug overdose deaths 0.53 0.52 0.61 1.34 2.64 5.89 Sex Male 0.58 0.60 0.70 1.83 3.83 8.63 Female 0.46 0.42 0.49 0.89 1.46 3.14 Race and Hispanic origin Non-Hispanic white 0.74 0.72 0.83 1.86 3.68 7.74 Non-Hispanic black 0.15 0.16 0.28 0.87 1.89 5.55 Hispanic 0.12 0.09 0.18 0.43 0.78 2.47 Public health region¹ 1 (CT, ME, MA, NH, RI, VT) 0.53 0.53 1.07 5.54 11.65 19.79 2 (NJ, NY, NYC) 0.39 0.39 0.63 1.12 2.91 7.88 3 (DE, DC, MD, PA, VA, WV) 0.70 0.64 0.94 1.95 3.88 11.87 4 (AL, FL, GA, KY, MS, NC, SC, TN) 0.67 0.66 0.71 1.48 2.79 5.70 5 (IL, IN, MI, MN, OH, WI) 0.57 0.52 0.55 1.83 4.16 9.63 6 (AR, LA, NM, OK, TX) 0.39 0.42 0.43 0.55 0.62 0.97 7 (IA, KS, MO, NE) 0.61 0.81 0.91 1.02 1.66 3.78 8 (CO, MT, ND, SD, UT, WY) 0.95 0.77 0.69 1.05 0.87 1.27 9 (AZ, CA, HI, NV) 0.33 0.24 0.26 0.29 0.42 0.81 10 (AK, ID, OR, WA) 0.43 0.53 0.48 0.58 0.56 0.89

¹Geographic regions defined by the U.S. Department of Health and Human Services (HHS), which are used for prevention, preparedness, and agency-wide coordination of HHS programs and policies. Region 1 includes Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, and Vermont; Region 2 includes New Jersey, New York, and New York City; Region 3 includes Delaware, District of Columbia, Maryland, Pennsylvania, Virginia, and West Virginia; Region 4 includes Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina, and Tennessee; Region 5 includes Illinois, Indiana, Michigan, Minnesota, Ohio, and Wisconsin; Region 6 includes Arkansas, Louisiana, New Mexico, Oklahoma, and Texas; Region 7 includes Iowa, Kansas, Missouri, and Nebraska; Region 8 includes Colorado, Montana, North Dakota, South Dakota, Utah, and Wyoming; Region 9 includes Arizona, California, Hawaii, and Nevada; Region 10 includes Alaska, Idaho, Oregon, and Washington. NOTES: Drug overdose deaths are identified using International Classification of Diseases, 10th Revision underlying cause-of-death codes X40–X44, X60–X64, X85, and Y10–Y14. Deaths may involve other drugs in addition to fentanyl. Caution should be used when comparing numbers across years. The reporting of at least one specific drug or drug class in the literal text, as identified by multiple cause-of-death codes T36–T50.8, improved from 75.0% of drug overdose deaths in 2011 to 85.4% in 2016. SOURCE: NCHS, National Vital Statistics System, Mortality files linked with death certificate literal text. 12 National Vital Statistics Reports, Vol. 68, No. 3, March 21, 2019

Table 3. Trends in age-adjusted rates for drug overdose deaths involving fentanyl, by sex, age, race and Hispanic origin, and public health region: United States, 2011–2016

Trend 1 Trend 2

Annual Annual 2011–2016 percent percent Average annual Characteristic Years change Years change percent change

All drug overdose deaths 2011–2013 8.5 2013–2016 113.3* 62.7* Sex Male 2011–2013 16.5 2013–2016 125.6* 73.2* Female 2011–2016 58.9* … … 58.9* Age group (years) 15–24 2011–2016 93.9* … … 93.9* 25–34 2011–2016 100.0* … … 100.0* 35–44 2011–2013 6.7 2013–2016 123.7* 66.4* 45–54 2011–2016 60.3* … … 60.3* 55–64 2011–2016 58.8* … … 58.8* 65 and over 2011–2016 41.6* … … 41.6* Race and Hispanic origin Non-Hispanic white 2011–2013 9.0 2013–2016 108.8* 61.0* Non-Hispanic black 2011–2016 140.6* … … 140.6* Hispanic 2011–2016 118.3* … … 118.3* Public health region¹ 1 (CT, ME, MA, NH, RI, VT) 2011–2016 113.9* … … 113.9* 2 (NJ, NY, NYC) 2011–2016 110.9* … … 110.9* 3 (DE, DC, MD, PA, VA, WV) 2011–2016 103.6* … … 103.6* 4 (AL, FL, GA, KY, MS, NC, SC, TN) 2011–2013 4.5 2013–2016 99.7* 54.1* 5 (IL, IN, MI, MN, OH, WI) 2011–2016 102.2* … … 102.2* 6 (AR, LA, NM, OK, TX) 2011–2016 20.8* … … 20.8* 7 (IA, KS, MO, NE) 2011–2016 47.8* … … 47.8* 8 (CO, MT, ND, SD, UT, WY) 2011–2016 7.1 … … 7.1 9 (AZ, CA, HI, NV) 2011–2014 –5.0 2014–2016 75.5 21.4 10 (AK, ID, OR, WA) 2011–2016 13.1* … … 13.1*

*Statistically significant increase at p value < 0.05. Trends in rates from 2011 through 2016 were evaluated using Joinpoint Regression Program (Version 4.6.0.0). … Category not applicable. ¹Geographic regions defined by the U.S. Department of Health and Human Services (HHS), which are used for prevention, preparedness, and agency-wide coordination of HHS programs and policies. Region 1 includes Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, and Vermont; Region 2 includes New Jersey, New York, and New York City; Region 3 includes Delaware, District of Columbia, Maryland, Pennsylvania, Virginia, and West Virginia; Region 4 includes Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina, and Tennessee; Region 5 includes Illinois, Indiana, Michigan, Minnesota, Ohio, and Wisconsin; Region 6 includes Arkansas, Louisiana, New Mexico, Oklahoma, and Texas; Region 7 includes Iowa, Kansas, Missouri, and Nebraska; Region 8 includes Colorado, Montana, North Dakota, South Dakota, Utah, and Wyoming; Region 9 includes Arizona, California, Hawaii, and Nevada; Region 10 includes Alaska, Idaho, Oregon, and Washington. NOTES: Drug overdose deaths are identified using International Classification of Diseases, 10th Revision underlying cause-of-death codes X40–X44, X60–X64, X85, and Y10–Y14. Deaths may involve other drugs in addition to fentanyl. SOURCE: NCHS, National Vital Statistics System, Mortality files linked with death certificate literal text. National Vital Statistics Reports, Vol. 68, No. 3, March 21, 2019 13

Technical Notes SUBLIMAZE, SUBSYS, SUFENTANIL*, TETRAHYDROFURANYLFENTANYL, THIOFENTANYL, Identification of fentanyl, fentanyl analogs, VALERYLFENTANYL* and misspellings on death certificate literal A comprehensive review for misspellings was conducted for terms with an asterisk because an exact pattern match of more text fields than five records was found in the literal text fields for National This report defines “drug overdoses involving fentanyl” Vital Statistics System—Mortality data for years 2010–2016. as a drug overdose death involving fentanyl itself, including The terms were grouped into broader fentanyl categories for prescription fentanyl and illicitly manufactured fentanyl, as well reporting purposes. The term groupings are detailed in Table I as any fentanyl metabolites, precursors, and analogs identified in according to the DMI methodology. the death certificate text. A search list for fentanyl was developed using the Scientific Methods for calculating and applying Working Group for the Analysis of Seized Drugs, which includes adjustment factor in trend analysis structurally confirmed reference materials generated by the United States Drug Enforcement Administration’s special testing The reporting of at least one specific drug involved in drug and research laboratory, and any monographs authored by overdose deaths improved from 75.0% in 2011 to 85.4% in 2016 the Forensic Drug Review and the Center for Forensic Science (2,22). Trend estimates may be impacted by the improvement in Research & Education (25). This list, combined with fentanyl reporting that occurred during the study period. To assess the analogs found in the U.S. Food and Drug Administration’s possible impact of the improved reporting of specific drugs in (FDA) Substance Registration System (26) as of August 2017, the years leading up to 2016, an adjustment factor was applied is listed below. This search list was used to conduct an initial to each rate (i.e., by year, sex, age, race and ethnicity, and public search of possible fentanyl terms mentioned in the literal text on health region) to calculate an adjusted rate. Drug specificity was death records from 2010 through 2016 using SAS Contextual determined for each year of the study as the percentage of drug Analysis software (18). If the term was found, a second analysis overdose deaths with at least one International Classification of was conducted to identify misspellings of the term. The National Diseases, 10th Revision (ICD–10) multiple cause-of-death code Center for Health Statistics and FDA's Drugs Mentioned with in the range of T36–T50.8. Drug specificity was calculated for Involvement (DMI) methodology was updated to include the new each demographic and geographic subgroup in years 2011– 2016 terms identified. by taking the number of drug overdose deaths with codes Fentanyl analogs identified in the literature, reports, and T36–T50.8 divided by the number of drug overdose deaths in a other sources are listed below: given region and year (Table II). For example, in 2011, there were 41,340 drug overdose deaths, and among these, 30,993 of the 3-METHYLFENTANYL*, 3-METHYLTHIOFENTANYL, deaths had a multiple-cause code of T36–T50.8, thus resulting 4-ANPP*, 4-CLORO-ISOBUTYLFENTANYL*, in 75.0% drug specificity among drug overdose deaths in 2011. 4-FLUOROBUTYRYLFENTANYL*, 4-FLUORO- The same calculation applies to those in specific subgroups; in ISOBUTYRYLFENTANYL*, 4-MeO-BUTYRYLFENTANYL*, 2011, there were 2,941 drug overdose deaths among Hispanic ABSTRAL, FENTANIL*, ACETYL-ALPHA- persons, and 2,300 drug overdose deaths had a multiple-cause METHYLFENTANYL, ACETYLFENTANYL*, code of T36–T50.8, resulting in 78.2% drug specificity. ACRYLFENTANYL*, ACRYLOYLFENTANYL*, ACTIQ, The adjustment factor (Table II) was calculated using the ALFENTANIL*, ALPHA-METHYLTHIOFENTANYL, following assumptions for each year and subgroup: 1) from BENTANYL, BETA-HYDROXY-3-METHYLFENTANYL, BETA- 2011 through 2015, the percentage of deaths with one or more HYDROXYFENTANYL, BETA-HYDROXYTHIOFENTANYL*, drugs specified was equal to the percentage in 2016, and 2) the BUTYRYLFENTANYL*, CARFENTANIL*, proportion of deaths involving fentanyl was the same for deaths CROTONYLFENTANYL, CYCLOPROPYLFENTANYL, that identified one or more specific drugs as for deaths that did DESPROPIONYL-2-FLUOROFENTANYL, not identify a specific drug. For example in 2011, there were DESPROPIONYLFENTANYL*, DURAGESIC*, FENTANYL*, 41,340 drug overdose deaths; the drug specificity was 75.0%, FENTORA, (2- or 3-) FURANYLFENTANYL*, IONSYS, and 1,663 deaths involved fentanyl for an age-adjusted rate ISOBUTYRYLFENTANYL*, LAZANDA, LOFENTANIL, (AAR) of 0.53 per 100,000 standard population. To adjust for META-FLUOROFENTANYL, METHOXYACETYLFENTANYL*, improved reporting: MIRFENTANYL, NORFENTANYL*, N-PHENETHYL-4- 1. Calculate the difference in percentage reporting in 2016 PIPERIDONE (NPP)*, OCFENTANIL, ONSOLIS, ORTHO- compared with 2011 (i.e., 85.4% – 75.0% = 10.4%). FLUOROFENTANYL*, PARA-CHLOROFENTANYL, 2. Multiply the difference in percentage reporting by PARA-CHLOROISOBUTYRFENTANYL, the total number of drug overdose deaths in 2011 PARA-FLUOROBUTYRYL-FENTANYL*, (i.e., 10.4% ∙ 41,340 = 4,299.36). PARA-FLUOROFENTANYL*, PARA- 3. Calculate the proportion of drug overdose deaths involving FLUOROISOBUTYRYLFENTANYL, PARA- fentanyl among drug overdose deaths with one or more METHODOXYBUTYRYLFENTANYL, REMIFENTANIL*, 14 National Vital Statistics Reports, Vol. 68, No. 3, March 21, 2019

drugs specified in 2011 (i.e., 1,663 / [75.0% ∙ 41,340] = 0.053636). 4. Multiply the results from step 2 by the results from step 3 (i.e., 4,299.36 ∙ 0.053636 = 230.6). 5. Calculate the adjustment factor by dividing the adjusted total drug overdose deaths involving fentanyl by the observed number of drug overdose deaths involving fentanyl (i.e., (1,663 + 230.6) / 1,663 = 1.14). 6. Calculate the adjusted AAR by multiplying the 2011 adjustment factor by the 2011 AAR rate (i.e., 0.53 ∙ 1.14 = 0.60). Table III shows the observed and adjusted age-adjusted death rates for each year by demographic and geographic group. The observed rates and number of drug overdose deaths involving any particular drug in any particular year should be considered the minimum number, as there may be additional deaths in which the drug was involved but not specified on the death certificate literal text. Observed and adjusted age-adjusted death rates resulted in similar findings after application of the adjustment factor (Table III). National Vital Statistics Reports, Vol. 68, No. 3, March 21, 2019 15

Table I. Fentanyl groupings, as detailed in the Drugs Mentioned with Involvement methodology identified from National Vital Statistics System—Mortality literal text, 2010–2016

Principal variant1 Search terms

FENTANYL ABSTRAL, ACETYL AND FENTANYL, ACTIQ, BENTANYL, DUEFENANYL, DURAGESIC, DURAHESIC, DURGESIC, F ENTANYL, FANTANIL, FANTANYL, FEBTANYL, FEDNTANYL, FENANYL, FENATANYL, FENATNYL, FENENYL, FENHANYL, FENNATYL, FENPANYL, FENRANYL, FENRTANYL, FENTAANYL, FENTABYL, FENTAHYL, FENTALYL, FENTALYN, FENTAMYL, FENTANAL, FENTANAYL, FENTANIE, FENTANIL, FENTANL, FENTANLY, FENTANOL, FENTANOLY, FENTANOYL, FENTANTL, FENTANTYL, FENTANUL, FENTANY, FENTANYAL, FENTANYL, FENTANYL AND ACETYL, FENTANYLAMENDED, FENTANYLANALOG, FENTANYLAND, FENTANYLC, FENTANYLE, FENTANYLINTOXICATION, FENTANYLTOXICITY, FENTANYTL, FENTARIYL, FENTARY, FENTATNYL, FENTAYNL, FENTENYL, FENTINGL, FENTINYL, FENTNANYL, FENTNAYL, FENTNYL, FENTONOL, FENTONYL, FENTORA, FENTYNAL, FENTYNOL, FENYANYL, FERTANY, FETAANYL, FETANYL, FETNYL, FEUTANYL, FNTANYL, FONTANYL, FRNTANYL, INTOXICATIONFENTANYL, LAZANDA, ONSOLIS, PARA FLUORO ISO BUTYRYL AND NONPRESCRIBED FENTANYL, PENTANYL, RENTANYL, SENTANYL, SUBSYS, TENTANYL .BETA.-HYDROXYTHIOFENTANYL B HYDROXYTHIOFENTANYL, BETA HYDROXYTHIOFENTANYL, BETAHYDROXYTHIOFENTANYL 3-METHYLFENTANYL METHY FENTANYL, METHYFENTANYL, METHYL FENTANYL, METHYLFENTANYL 4-FLUOROBUTYRFENTANYL F BF, FENTANYL ANALOGUES FURANYL PARAFLUROBUTYRYL AND DESPROPIONYL, FIBF, FLOROBUTYRYL FENTANYL, FLUOROBUTYLFENTANYL, FLUOROBUTYRFENTANYL, FLUOROBUTYRYL FENTANYL, P FLUOROBUTYRYL FENTANYL, P FLUOROBUTYRYL FETANYL, PARA FLUOROBUTRYL FENTANYL, PARA FLUOROBUTYRL FENTANYL, PARA FLUOROBUTYRYL FENTANYL, PARA FLUOROBUTYRYL FIBF, PARA FLUOROBUTYRYL PARA FLUOROISOBUTYRYL FENTANYL, PARA FLUOROBUTYRYL TENTANY, PARA FLUOROBUTYRYLFENTANYL, PARA FLUOROBUTYRYRL PARA FLUOROISOBUTYRYL FENTANYL, PARA FLUROBUTYRYL F, PARA FLUROBUTYRYL FENTANYL, PARAFLUOROBUTRYL FENTANYL, PARAFLUOROBUTYRL FENTANYL, PARAFLUOROBUTYRYL FENTANYL 4-FLUOROISOBUTYRYLFENTANYL DESPROPIONYL AND FLUORISOBUTYRYL FENTANYL, FLOUROISOBUTYRYL FENTANYL, FLUORISOBUTYRLFENTANYL, FLUORISOBUTYRYLFENTANYL, FLUORO ISOBUTYRYL FENTANYL, FLUOROISOBUTRYRLFENTANYL, FLUOROISOBUTYRFENTANYL, FLUOROISOBUTYRL FENTANYL, FLUOROISOBUTYRYL FENTANYL, FLUOROISOBUTYRYLFENTANYL, FLURISOBUTYRYLFENTANYL, FLUROISOBUTYRYL FENTANYL, FLUROISOBUTYRYLFENTANYL, P FLUORO ISOBUTYRYL FENTANYL, P FLUOROISOBUTYRL FENTANYL, P FLUROISOBUTYRYL FENTANYL, PARA FLOURO ISOBUTYRYL FENTANYL, PARA FLUORO ISO BUTYRL FENTANYL, PARA FLUORO ISO BUTYRYL AND NONPRESCRIBED FENTANYL, PARA FLUORO ISO BUTYRYL FENTANYL, PARA FLUORO ISOBUTYL FENTANYL, PARA FLUORO ISOBUTYRL FENTANYL, PARA FLUORO ISOBUTYRYL FENTANYL, PARA FLUORO ISOBUTYRYL FENTNAYL, PARA FLUOROBUTYRYL PARA FLUOROISOBUTYRYL FENTANYL, PARA FLUOROBUTYRYRL PARA FLUOROISOBUTYRYL FENTANYL, PARA FLUOROISOBTYRYLFENTANYL, PARA FLUOROISOBUTRYL FENTANYL, PARA FLUOROISOBUTYRLFENTANYL, PARA FLUOROISOBUTYRYIFENTANYL, PARA FLUOROISOBUTYRYL FENTANYL, PARA FLUOROISOBUTYRYLFENTANYL, PARA FLURO ISO BUTYRL FENTANYL, PARAFLUORO ISO BUTYRYL FENTANYL, PARAFLUORO ISP BUTYRYL FENTANYL, PARAFLUOROISOBUTURYLFENTANYL, PARAFLUOROISOBUTYRYL FENTANYL, PARAFLUOROISOBUTYRYLFENTANYL, PARAFLUROISOBUTYRYLFENTANYL 4-METHOXYBUTYRFENTANYL METHOXY BUTYRYL FENTANYL ACETYLFENTANYL AACETYL FENTANYL, ACETANYL FENTANYL, ACETLY FENTANYL, ACETLYFENTANYL, ACETY FENTANYL, ACETYFENTANYL, ACETYFENTANYL N PHENETHYL PIPERIDYL ACETANILIDE, ACETYL AND FENTANYL, ACETYL FENTANTYL, ACETYL FENTANYAL, ACETYL FENTANYL, ACETYL FENTANYL N PHENETHYL PIPER IDYL ACETANILIDE, ACETYL FENTANYL N PHENETHYL PIPERIDYL ACETANILIDE, ACETYL FENTANYL PHENETHYL PIPERIDYL ACETANILLDE, ACETYL FENTANYLC, ACETYL FENTANYTL, ACETYL FENTENYL, ACETYL FURANYL FENTANYL, ACETYLE FENTANYL, ACETYLEFENTANYL, ACETYLFENTAL, ACETYLFENTAL PHENETHYL PIPERIDYL ACETANILIDE, ACETYLFENTANLY, ACETYLFENTANYL, ACETYLFENTANYL N PHENETHYL PIPERIDYL ACETANILIDE, ACETYLFENTNYL, ACETYLFETANYL, ACETYLFONTANYL N PHENETHYL PIPERIDYL ACE, ACTEYL FENTANYL, FENTANYL AND ACETYL, N PHENETHY PIPER IDYL ACETANILIDE, N PHENETHY PIPERIDY ACETANILIDE, N PHENETHYL PIPER IDYL ACETANILIDE, N PHENETHYL PIPERDYL ACETANILIDE, N PHENETHYL PIPERIDYL ACETANILIDE, PHENETHYL PIPERIDYL ACETANILIDE, TYL FENTANYL N PHENETHYL PIPERIDYL ACETANILIDE ACRYLFENTANYL ACRYIFENTANYL, ACRYL FENTANYL, ACRYLFENTANYL ALFENTANIL ALFENTANIL BUTYRFENTANYL BUTRYL FENTANYL, BUTYL FENTANYL, BUTYR FENTANYL, BUTYRFENTANYL, BUTYRYL FENTANYL, BUTYRYLFENTANUL, BUTYRYLFENTANYL CARFENTANIL CARENTANIL, CARENTANYL, CARFENTAIL, CARFENTANI, CARFENTANIL, CARFENTANILI, CARFENTANILTOXICITY, CARFENTANTANIL, CARFENTANYL, CARFENTENIL, CARFENTIL, CARFENTINAL, CARFENTINIL, CARRENTANIL, CARTENTANIL DEPROPIONYL FLUOROFENTANYL DESPROPIONYL FLUOROFENTANYL

See footnotes at end of table. 16 National Vital Statistics Reports, Vol. 68, No. 3, March 21, 2019

Table I. Fentanyl groupings, as detailed in the Drugs Mentioned with Involvement methodology identified from National Vital Statistics System—Mortality literal text, 2010–2016—Con.

Principal variant1 Search terms

DEPROPIONYLFENTANYL ANILINE N PHENYTHYLPIPERIDINE, ANILINO N PHENETHYIPIPERIDINE, ANILINO N PHENETHYL PIPERIDINE, ANILINO N PHENETHYLPIPENDINE, ANILINO N PHENETHYLPIPERDINE, ANILINO N PHENETHYLPIPERIDINE, ANILINO PHENETHYPIPERIDINE, ANILIO N PHENETHYLPIPERIDINE, ANILO N PHENETHYLPIPERIDINE, ANPP, DEPROPIONLFENTANYL, DEPROPIONYL FENTANYL, DEPROPIONYLFENTANYL, DESOROPIONYL FENTANYL, DESPROPIONY FENTANYL, DESPROPIONYFENTANYL, DESPROPIONYL AND FLUORISOBUTYRYL FENTANYL, DESPROPIONYL ANILIO N PHENETHYLPIPERIDINE, DESPROPIONYL FENTANYL, DESPROPIONYLFENTANYL, DESPROPIOYL FENTANYL, DESPROPLONYL FENTNYL, DESPROPRIONYL FENTANYL, DESPROPRIONYLFENTANYL, FENTANYL ANALOGUES FURANYL PARAFLUROBUTYRYL AND DESPROPIONYL, N PHENETHYL PIPERIDINE, N PHENYL PHENYLETHYL PIPERIDIN AMINE FURANYLFENTANYL+ ACETYL FURANYL FENTANYL, DURANYLFENTANYL, FENTANYL ANALOGUES FURANYL PARAFLUROBUTYRYL AND DESPROPIONYL, FERANYL FENTANYL, FUNANYL FENTANYL, FURANULFENTANYL, FURANY FENTANUL, FURANY FENTANYL, FURANYFENTANYL, FURANYIFENTANYL, FURANYL FENTANYL, FURANYLFANTANYL, FURANYLFENTANTL, FURANYLFENTANYL, FURANYLFENTANYLM, FURANYLTENTANYAL, FURANYLTENTANYL, FURAYLFENTANY, FURAYLFENTANYL, FURFANYLFENTANYL, FURNYL FENTAYL, FURTANYL FENTANYL, FURYL FENTANYL, TURANYL FENTANYL ISOBUTYRFENTANYL ISOBUTYRYLFENTANYL METHOXYACETYLFENTANYL METHOXYACETYL FENTANYL METHYLFENTANYL+ CIS METHYLFENTANYL NORALFENTANIL NORALFENTANIL NORFENTANYL NORENTANYL, NORFENTANLY, NORFENTANYL, NORFETANYL, NORPHENTANYL ORTHO-FLUOROFENTANYL ORTHO FLUOROFENTANYL P-FLUOROFENTANYL FLUORA FENTANYL, FLUOROFENTANYL, FLURODENTANYL, FLUROFENTANYL, FLUROROFENTANYL, PARA FLUROFENTANYL, PARAFLOUROFENTANYL, PARAFLUORO FENTANYL REMIFENTANIL REMIFENTANIL, REMIFENTANYL SUFENTANIL SUFENTANIL AMBIGUOUS (FENTANYL or TEGAFUR) FENTALY, FENTAYL, FENTYAL, FENTYL AMBIGUOUS (NORALFENTANIL or NORFENTANYL) NOAFENTANYL

1The overarching label assigned to a drug, a drug class, or exposure not otherwise specified in the Drugs Mentioned with Involvement methodology. For example, terms such as “COCAIEN,” “COCAINE CRACK,” “COCAINE HYDROCHLORIDE,” and “COCAINETOXICITY” are all mapped to the principal variant “COCAINE.” In the case of drug overdose deaths involving fentanyl, all of the principal variants in this table were used to calculate the numbers and rates presented in this report. SOURCE: NCHS, National Vital Statistics System, Mortality files linked with death certificate literal text. National Vital Statistics Reports, Vol. 68, No. 3, March 21, 2019 17 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 2016 1.00 1.03 1.03 1.02 1.03 1.02 1.00 1.03 1.03 1.00 1.03 1.04 1.02 1.03 1.03 1.02 1.04 1.06 1.03 1.02 1.00 1.02 2015 1.00 1.04 1.06 1.07 1.06 1.04 1.01 1.05 1.08 1.00 1.05 1.04 1.05 1.02 1.07 1.07 1.06 1.12 1.07 1.06 1.04 1.04 2014 Adjustment factor 1.03 1.06 1.10 1.11 1.10 1.08 1.02 1.05 1.12 1.01 1.06 1.06 1.09 1.03 1.12 1.16 1.10 1.16 1.10 1.08 1.06 1.09 2013 1.09 1.10 1.12 1.12 1.13 1.11 1.02 1.07 1.15 1.11 1.11 1.08 1.12 1.07 1.13 1.17 1.13 1.19 1.12 1.09 1.07 1.08 2012 1.09 1.13 1.14 1.10 1.14 1.12 1.03 1.09 1.16 1.09 1.12 1.09 1.15 1.07 1.16 1.19 1.14 1.21 1.14 1.17 1.06 1.08 2011 85.3 84.6 85.4 83.2 88.4 93.4 92.1 88.1 88.5 98.9 87.2 90.2 86.0 76.0 85.5 83.8 84.8 89.3 84.8 81.8 84.9 84.7 2016 84.9 82.4 83.1 81.2 85.6 91.8 92.1 85.3 86.1 98.8 84.8 86.8 84.1 73.6 82.8 82.0 81.7 83.9 82.5 79.9 84.7 83.3 2015 85.4 79.8 80.7 77.7 83.8 90.4 91.0 84.7 82.5 98.9 83.2 86.7 82.0 74.3 80.2 78.4 79.7 79.9 79.3 76.9 81.7 81.5 2014 Percent 82.5 76.5 77.9 75.3 84.5 88.1 90.0 83.1 79.8 97.4 81.9 85.2 79.2 74.1 76.5 72.4 77.0 76.9 77.0 76.0 80.0 77.9 2013 International Classification of Diseases, 10th Revision [ICD–10] underlying cause-of-death codes X40–X44, X60–X64, X85, and Y10–Y14) with ICD–10 multiple 74.7 76.0 74.3 82.6 86.2 90.3 80.4 78.4 89.0 78.7 83.5 76.4 71.2 75.4 71.7 74.8 74.9 75.7 74.8 79.2 78.4 78.1 2012 73.9 75.0 75.8 80.7 84.5 89.8 78.2 77.5 90.6 77.9 82.5 75.1 70.8 73.8 70.4 74.2 73.5 74.4 69.9 79.8 78.2 78.0 2011 Sex Age group (years) Public health region ¹ Characteristic Race and Hispanic origin Non-Hispanic white All drug overdose deaths 9 (AZ, CA, HI, NV) Non-Hispanic black Male 10 (AK, ID, OR, WA) Hispanic Female 1 (CT, ME, MA, NH, RI, VT) 1 (CT, 15–24 2 (NJ, NY, NYC) 2 (NJ, NY, 25–34 3 (DE, DC, MD, PA, VA, WV) VA, 3 (DE, DC, MD, PA, 35–44 4 (AL, FL, GA, KY, MS, NC, SC, TN) 4 (AL, FL, GA, KY, 45–54 5 (IL, IN, MI, MN, OH, WI) 55–64 6 (AR, LA, NM, OK, TX) 65 and over 7 (IA, KS, MO, NE) 8 (CO, MT, ND, SD, UT, WY) ND, SD, UT, 8 (CO, MT, Table II. Percent of drug overdose deaths with drugs specified, by sex, age, race and Hispanic origin, and public health region: United States, 2011–2016 and public health region: United States, race and Hispanic origin, age, by sex, of drug overdose deaths with drugs specified, Percent II. Table ¹Geographic regions defined by the U.S. Department of Health and Human Services (HHS), which are used for prevention, preparedness, and agency-wide coordination of HHS programs policies. Region 1 includes Connecticut, Maine, City; Region 3 includes Delaware, District of Columbia, Maryland,Virginia; 4 Pennsylvania, Virginia, and West and New York New York, Region 2 includes New Jersey, Massachusetts, New Hampshire, Rhode Island, and Vermont; Region 5 includes Illinois, Indiana, Michigan, Minnesota, Ohio, and Wisconsin; 6 Arkansas, Louisiana, New Mexico, Oklahoma, Mississippi, North Carolina, South and Tennessee; Alabama, Florida, Georgia, Kentucky, Montana, North Dakota, South Utah, and Wyoming; Region 9 includes Arizona, California, Hawaii, Nevada; 10 Alaska, Region 7 includes Iowa, Kansas, Missouri, and Nebraska; 8 Colorado, Texas; Idaho, Oregon, and Washington. NOTE: Drug specificity is calculated by taking the number of drug overdose deaths ( cause-of-death codes T30–T50.8, divided by the number of drug overdose deaths in a given region and year. and year. cause-of-death codes T30–T50.8, divided by the number of drug overdose deaths in a given region text. SOURCE: NCHS, National Vital Statistics System, Mortality files linked with death certificate literal 18 National Vital Statistics Reports, Vol. 68, No. 3, March 21, 2019 – – ( * ) – ( * ) – ( * ) – ( * ) – ( * ) – ( * ) – ( * ) – ( * ) – ( * ) – ( * ) – ( * ) – ( * ) – ( * ) – ( * ) – ( * ) 1 (2013) * 1 (2013) * 1 (2013) * 1 (2014) 1 (2013) * 1 (2013) * Number of final model (time point) joinpoints in 9.63 4.78 0.97 0.61 5.89 3.78 7.74 8.63 1.27 5.55 3.14 0.81 2.47 4.42 0.89 7.88 8.25 5.70 2016 19.79 13.38 11.40 11.87 4.43 2.25 0.64 0.28 2.71 1.69 3.78 3.92 0.87 1.95 1.51 0.43 0.80 2.17 0.56 6.23 3.02 5.06 4.00 3.86 2.85 2015 11.66 2.05 1.30 0.59 0.20 1.42 1.06 1.97 1.91 1.05 0.92 0.96 0.31 0.44 1.08 0.58 5.53 2.95 1.16 2.61 1.99 2.38 1.58 2014 0.64 0.91 0.46 0.16 0.67 0.98 0.92 0.75 0.72 0.29 0.54 0.29 0.19 0.39 0.49 1.09 1.05 0.67 1.10 0.96 1.39 0.82 2013 Adjusted death rate 0.62 0.76 0.46 0.15 0.59 0.87 0.81 0.66 0.85 0.17 0.49 0.26 0.10 0.28 0.54 0.58 0.88 0.42 0.98 0.68 1.28 0.77 2012 0.70 0.46 0.14 0.60 0.66 0.85 0.65 1.04 0.17 0.53 0.37 0.13 0.33 0.45 0.58 0.89 0.43 1.08 0.76 1.29 0.79 0.79 2011 – – ( * ) – ( * ) – ( * ) – ( * ) – ( * ) – ( * ) – ( * ) – ( * ) – ( * ) – ( * ) – ( * ) – ( * ) – ( * ) – ( * ) – ( * ) 1 (2014) 1 (2013) * 1 (2013) * 1 (2013) * 1 (2013) * 1 (2013) * Number of final model (time point) joinpoints in 9.63 0.97 0.61 5.89 3.78 7.74 8.63 1.27 5.55 3.14 0.81 2.47 4.42 0.89 7.88 8.25 5.70 4.78 2016 19.79 13.38 11.40 11.87 0.62 0.28 2.64 1.66 3.68 3.83 0.87 1.89 1.46 0.42 0.78 2.11 0.56 6.10 2.91 4.90 3.88 3.72 2.79 2.19 4.16 2015 11.65 0.55 0.20 1.34 1.02 1.86 1.83 1.05 0.87 0.89 0.29 0.43 1.03 0.58 5.54 2.81 1.12 2.45 1.95 2.23 1.48 1.22 1.83 2014 0.43 0.15 0.61 0.91 0.83 0.70 0.69 0.28 0.49 0.26 0.18 0.36 0.48 1.07 0.97 0.63 0.99 0.94 1.26 0.71 0.83 0.55 2013 Observed death rate 0.42 0.14 0.52 0.81 0.72 0.60 0.77 0.16 0.42 0.24 0.09 0.25 0.53 0.53 0.78 0.39 0.86 0.64 1.12 0.66 0.68 0.52 2012 0.39 0.13 0.53 0.61 0.74 0.58 0.95 0.15 0.46 0.33 0.12 0.29 0.43 0.53 0.78 0.39 0.93 0.70 1.13 0.67 0.69 0.57 2011 Sex Age group (years) Public health region ¹ Characteristic Race and Hispanic origin 6 (AR, LA, NM, OK, TX) 65 and over All drug overdose deaths 7 (IA, KS, MO, NE) Non-Hispanic white Male 8 (CO, MT, ND, SD, UT, WY) ND, SD, UT, 8 (CO, MT, Non-Hispanic black Female 9 (AZ, CA, HI, NV) Hispanic 15–24 10 (AK, ID, OR, WA) 1 (CT, ME, MA, NH, RI, VT) 1 (CT, 25–34 2 (NJ, NY, NYC) 2 (NJ, NY, 35–44 3 (DE, DC, MD, PA, VA, WV) VA, 3 (DE, DC, MD, PA, 45–54 4 (AL, FL, GA, KY, MS, NC, SC, TN) 4 (AL, FL, GA, KY, 55–64 5 (IL, IN, MI, MN, OH, WI) Table III. Rates of drug overdose deaths involving fentanyl, observed and adjusted for improved specificity, by sex, age, race and Hispanic origin, and public health region: race and Hispanic origin, age, by sex, observed Rates of drug overdose and adjusted for improved deaths involving fentanyl, specificity, III. Table 2011–2016 United States, 4.6.0.0). in rates from 2011 through 2016 were evaluated using Joinpoint Regression Program (Version *Statistically significant increases at p value < 0.05. Trends – Quantity zero. ¹Geographic regions defined by the U.S. Department of Health and Human Services (HHS), which are used for prevention, preparedness, and agency-wide coordination of HHS programs policies. Region 1 includes Connecticut, Maine, City; Region 3 includes Delaware, District of Columbia, Maryland,Virginia; 4 Pennsylvania, Virginia, and West and New York New York, Region 2 includes New Jersey, Massachusetts, New Hampshire, Rhode Island, and Vermont; Region 5 includes Illinois, Indiana, Michigan, Minnesota, Ohio, and Wisconsin; 6 Arkansas, Louisiana, New Mexico, Oklahoma, Mississippi, North Carolina, South and Tennessee; Alabama, Florida, Georgia, Kentucky, Montana, North Dakota, South Utah, and Wyoming; Region 9 includes Arizona, California, Hawaii, Nevada; 10 Alaska, Region 7 includes Iowa, Kansas, Missouri, and Nebraska; 8 Colorado, Texas; Idaho, Oregon, and Washington. NOTES: Drug overdose deaths are identified using International Classification of Diseases, 10th Revision underlying cause-of-death codes X40–X44, X60–X64, X85, and Y10–Y14. Deaths may involve other drugs in addition to fentanyl. De ath rates age adjusted. text. 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National Vital Statistics Reports, Vol. 68, No. 3, March 21, 2019

Contents Acknowledgments Abstract ...... 1 The authors would like to acknowledge the contributions of Lauren Rossen, Introduction ...... 1 Katherine E. Irimata, and Donald Malec of the National Center for Health Statistics, Methods ...... 2 for their guidance on the trends analysis; and Bruce Goldberger at the University Data sources ...... 2 of Florida College of Medicine and Barry Logan at NMS Labs, for their expert Identifying drug overdose deaths involving fentanyl...... 2 toxicological input on fentanyl terms, analogs, derivatives, and other forms. Analysis ...... 2 Assessment for improved reporting on death certificates ...... 3 Results ...... 3 Number and percentage of drug overdose deaths involving fentanyl ...... 3 Crude and age-adjusted rates of drug overdose deaths involving fentanyl ...... 3 Rates of drug overdose deaths involving fentanyl by sex of decedent ...... 3 Rates of drug overdose deaths involving fentanyl by age group...... 3 Rates of drug overdose deaths involving fentanyl by race and ethnicity .....4 Rates of drug overdose deaths involving fentanyl by public health region...... 4 Discussion ...... 4 Limitations ...... 5 Conclusion ...... 7 References ...... 7 List of Detailed Tables ...... 8 Technical Notes ...... 13

Suggested citation Copyright information National Center for Health Statistics Spencer MR, Warner M, Bastian BA, Trinidad All material appearing in this report is in Jennifer H. Madans, Ph.D., Acting Director JP, Hedegaard H. Drug overdose deaths the public domain and may be reproduced Amy M. Branum, Ph.D., Acting Associate Director for involving fentanyl, 2011–2016. National Vital or copied without permission; citation as to Science Statistics Reports; vol 68 no 3. Hyattsville, MD: source, however, is appreciated. Office of Analysis and Epidemiology National Center for Health Statistics. 2019. Irma E. Arispe, Ph.D., Director Irma E. Arispe, Ph.D., Acting Associate Director for Science Division of Vital Statistics Steven Schwartz, Ph.D., Director Hanyu Ni, Ph.D., M.P.H., Associate Director for Science

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